Relationship of Serum 25-Hydroxyvitamin D Concentrations, Diabetes, Vitamin D Receptor Gene Polymorphisms and Incident Venous Thromboembolism

Abstract

Aims

The association between vitamin D and the risk of venous thromboembolism (VTE) remains inconclusive. We aimed to explore the association of serum 25-hydroxyvitamin D (25OHD) with incident VTE among participants with and without diabetes, and examine the modifying effect of genetic susceptibility of VTE and vitamin D receptor (VDR) gene polymorphisms on this association.

Materials and Methods

A total of 378,082 participants free of VTE at baseline from the UK Biobank were included. Serum 25OHD concentrations were measured by the chemiluminescent immunoassay method. The primary outcome was incident VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE). The genetic risks of VTE were estimated using 297 single nucleotide polymorphisms (SNPs) associated with VTE. The VDR gene polymorphisms included SNPs of rs7975232, rs1544410, rs2228570 and rs731236.

Results

During a median follow-up duration of 12.5 years, 10,645 VTE cases were recorded. Serum 25OHD had a significantly stronger inverse association with incident VTE in participants with diabetes (per SD increment, adjusted HR: 0.87; 95% CI: 0.81–0.93) than in those without diabetes (per SD increment, adjusted HR: 0.97; 95% CI: 0.95–0.99; p-interaction = 0.003). Similar trends were found for incident DVT and PE. Among participants with diabetes, the genetic risk of VTE did not significantly modify the association between serum 25OHD and incident VTE (p-interaction = 0.607). However, a stronger inverse association of serum 25OHD with incident VTE was found in the VDR rs2228570 AA genotype (vs. GG/AG; p-interaction = 0.031).

Conclusions

Serum 25OHD was inversely associated with the risk of VTE, especially among participants with diabetes, regardless of genetic risks of VTE.